DPH5

Chr 1AR

diphthamide biosynthesis 5

Also known as: AD-018, CGI-30, HSPC143, NEDSFF, NPD015

This gene encodes a component of the diphthamide synthesis pathway. Diphthamide is a post-translationally modified histidine residue found only on translation elongation factor 2. It is conserved from archaebacteria to humans, and is targeted by diphtheria toxin and Pseudomonas exotoxin A to halt cellular protein synthesis. The yeast and Chinese hamster homologs of this protein catalyze the trimethylation of the histidine residue on elongation factor 2, resulting in a diphthine moiety that is subsequently amidated to yield diphthamide. Multiple transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Jul 2008]

OMIMResearchGenerating clinical summary…
DNmechanismARLOEUF 1.271 OMIM phenotype
Clinical SummaryDPH5
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Gene-Disease Validity (ClinGen)
neurodevelopmental disorder with short stature, prominent forehead, and feeding difficulties · ARLimited

Limited evidence — not for standalone diagnostic reporting

Population Constraint (gnomAD)
Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.
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ClinVar Variants
4 unique Pathogenic / Likely Pathogenic· 37 VUS of 54 total submissions

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

Tolerant — LoF & missense variants common in population
LoF Constraint?
1.27LOEUF
pLI 0.000
Z-score 0.82
OE 0.77 (0.481.27)
Tolerant

Highly tolerant — LoF variants common in population

Missense Constraint?
0.48Z-score
OE missense 0.89 (0.771.03)
131 obs / 147.4 exp
Tolerant

Mild missense constraint

Observed / Expected Ratios?
LoF OE?0.77 (0.481.27)
00.351.4
Missense OE?0.89 (0.771.03)
00.61.4
Synonymous OE?1.06
01.21.6
LoF obs/exp: 11 / 14.3Missense obs/exp: 131 / 147.4Syn Z: -0.36
Curated Mechanism (G2P)Gene2Phenotype (DDG2P) ↗
moderateDPH5-related neurodevelopmental disorderOTHERAR

This gene — mechanism propensity

Predictions shown for reference only — model trained on dominant genes, not applicable to AR conditions.

DN
0.6356th %ile
GOF
0.3986th %ile
LOF
0.3260th %ile

The Badonyi & Marsh prediction model was trained exclusively on dominant disease genes. Predictions are not reliable for genes with autosomal recessive inheritance and are shown at reduced opacity for reference only.

Predictions from Badonyi M, Marsh JA. PLoS ONE. 2024;19(8):e0307312.

ClinVar Variant Classifications

54 submitted variants in ClinVar

Classification Summary

Pathogenic2
Likely Pathogenic2
VUS37
2
Pathogenic
2
Likely Pathogenic
37
VUS

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
1
1
0
0
2
Likely Pathogenic
1
1
0
0
2
VUS
1
36
0
0
37
Likely Benign
0
0
0
0
0
Benign
0
0
0
0
0
Total3380041

LoF = frameshift, stop gained/lost, canonical splice · Counts from ClinVar esearch · Updated hourly

View in ClinVar →

8 pathogenic / likely-pathogenic (of 14) ClinVar copy-number / structural variants overlap DPH5 — these span large chromosomal regions, not the gene specifically, and are excluded from the counts above. Explore in CNV tools →

Protein Context — Lollipop Plot

DPH5 · protein map & ClinVar variants

Showing all ClinVar variants across the protein. Search a specific variant to highlight its position.

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

No active trials found for this gene.

Search ClinicalTrials.gov →